Abstract：
Lobeline (LOB), a naturally occurring alkaloid, has a broad spectrum of pharmacological activities and therapeutic potential, including applications in central nervous system disorders, drug misuse, multidrug resistance, smoking cessation, depression, and epilepsy. LOB represents a promising compound for developing treatments in various medical fields. However, despite extensive pharmacological profiling, the biophysical interaction between the LOB and proteins remains largely unexplored. In the current article, a range of complementary photophysical and cheminformatics methodologies were applied to study the interaction mechanism between LOB and the carrier protein HSA. Steady-state fluorescence and fluorescence lifetime experiments confirmed the static-quenching mechanisms in the HSA-LOB system. \"K\" (binding constant) of the HSA-LOB system was determined to be 105 M-1, with a single preferable binding site in HSA. The forces governing the HSA-LOB stable complex were analyzed by thermodynamic parameters and electrostatic contribution. The research also investigated how various metal ions affect complex binding. Site-specific binding studies depict Site I as probable binding in HSA by LOB. We conducted synchronous fluorescence, 3D fluorescence, and circular dichroism studies to explore the structural alteration occurring in the microenvironment of amino acids. To understand the robustness of the HSA-LOB complex, we used theoretical approaches, including molecular docking and MD simulations, and analyzed the principal component analysis and free energy landscape. These comprehensive studies of the structural features of biomolecules in ligand binding are of paramount importance for designing targeted drugs and delivery systems.
摘要：
Lobeline(LOB),一种天然存在的生物碱，具有广泛的药理活性和治疗潜力，包括在中枢神经系统疾病中的应用，药物滥用,多药耐药,戒烟,抑郁症,和癫痫。LOB代表用于在各种医学领域开发治疗的有前途的化合物。然而,尽管广泛的药理学分析，LOB和蛋白质之间的生物物理相互作用仍未被探索。在当前的文章中，应用一系列互补的光物理和化学信息学方法研究了LOB与载体蛋白HSA之间的相互作用机制。稳态荧光和荧光寿命实验证实了HSA-LOB系统中的静态猝灭机制。HSA-LOB系统的“K”(结合常数)被确定为105M-1,在HSA中具有单个优选的结合位点。通过热力学参数和静电贡献分析了控制HSA-LOB稳定复合物的力。该研究还研究了各种金属离子如何影响络合物结合。位点特异性结合研究将位点I描述为通过LOB在HSA中的可能结合。我们进行了同步荧光，3D荧光,和圆二色性研究，以探索氨基酸微环境中发生的结构改变。要了解HSA-LOB复合物的鲁棒性，我们使用了理论方法，包括分子对接和MD模拟，主成分分析和自由能景观分析。这些对配体结合中生物分子的结构特征的全面研究对于设计靶向药物和递送系统至关重要。
